Both analytical chemistry and process flow control make wide use of liquid chromatographs to analyze solutions. The output of the liquid chromatograph may be applied to a mass spectrometer, or any one of a variety of vapor phase detectors such as those utilizing photoionization, electron capture or flame ionization techniques, but to do so, the solution must be vaporized. Many methods are known for vaporizing solids and liquids for use with these devices, but these techniques cannot be generally applied to the vaporization of solutions of non-volatile solutes without producing uncontrolled chemical modification of the solute, such as pyrolysis, or without causing the solute to "salt out" on solid surfaces. In addition, various techniques applicable to some types of detection and analytical chemistry cannot be applied to others because of solvent interference or matrix effects. In addition, certain large, thermally labile molecules are difficult to vaporize inasmuch as they fragment in an uncontrolled manner when subjected to excessive heat.
The need to convert materials to be analyzed or detected into an ion vapor has been a problem in the field of the analytical chemistry for which no completely satisfactory solution has heretofore existed. Gaseous compounds or compounds which can be thermally vaporized without decomposition can usually be converted to an ion vapor relatively easily by heating the compound to vaporize it if it is not a gas, and either bombarding the compound in its gaseous state with a beam of electrons (electron impact ionization) or by introducing chemically-reactive ions into the gas (chemical ionization). However, many compounds are not sufficiently volatile at ambient temperatures to form a gas suitable for either electron-impact ionization or chemical ionization, and moreover, may be decomposed when heated so that they cannot be vaporized thermally. Among the compounds which cannot be converted into an ion vapor by these conventional techniques are many which are of biological, medical and pharmaceutical interest.
A number of special techniques have been developed to generate an ion vapor from compounds of low volatility. These techniques include field desorption, plasma desorption, rapid evaporation from inert surfaces and secondary ionization mass spectrometry. In addition to these, other techniques may be found in Analytical Chemistry, vol. 51, pp. 682A-701A (June 1979). None of these techniques is without its limitations, however, and a need still exists for an improved method for obtaining mass spectra of involatile, heat sensitive materials.
The problems of forming an ion vapor of involatile and heat sensitive compounds become particularly acute when it is attempted to use a mass spectrometer to analyze the effluent of a liquid chromatograph. Liquid chromatographs are widely used to separate mixtures into the component compounds, and find particular application when one or more of the component compounds is too involatile to permit the mixture to be separated with a conventional gas chromatograph. Although mass spectrometers have been widely and successfully interfaced to gas chromatographs to permit mass spectra to be taken of compounds in gaseous effluent from the chromatograph, efforts to interface liquid chromatograph to mass spectrometers, have been less successful, in part because compounds eluted from the liquid chromatograph are frequently involatile and heat sensitive and thus not amenable to conversion into ion vapor by conventional techniques. Moreover, the compounds to be analyzed from a liquid chromatograph are dissolved in a volatile solvent, which tends to reduce the ionization efficiency of the mass spectrometer even further with respect to the solute compounds of interest since solvent vapor is generally ionized along with the solute compounds and the solvent is typically in a much greater concentration then the solute compounds.
One attempt to interface the mass spectrometer to a liquid chromatograph is described in the U.S. Pat. No. 4,160,161 to Horton. Effluent from a liquid chromatograph is injected into an ion chamber maintained at a low pressure by means of a needle which projects into the chamber. The low pressure in the chamber pulls the solvent and solute through the needle and sprays it into the chamber. A laser or other heat source may be utilized to prevent the effluent from freezing as it flows through the needle and to provide heat to the effluent within the ion chamber. The needle is maintained at a high voltage by a high voltage power supply so that the spray carries a charge. The solvent evaporates in a low pressure environment, reducing the size of the charge droplets until ideally only the ions remain. However, the application of high voltage in the presence of gases and vapor may cause the vapor phase to break down and become electrically conductive. The resultant uncontrolled electrical discharges in the ion chamber leads to unstable and erratic behavior.
Another method and apparatus for connecting a liquid chromatograph directly to a mass spectrometer was disclosed in U.S. Pat. No. 4,298,795 to Takeuchi et al. The patent describes a process whereby the liquid effluent is nebulized in a high temperature environment of approximately 300.degree.. The second capillary tube is utilized to draw the molecules of interest into the mass spectrometer while an off axis pump withdraws the bulk of the solute that is not drawn into the second capillary. In addition, a heating means is provided for the second capillary to prevent recondensation of the effluent on the internal walls of the capillary.
Applicants invention may be distinguished from each of the above references inasmuch as the present application uses a thermal spray to partially vaporize a solution. By partially vaporizing the solution within a capillary tube, the expanding vapor phase of the solution is used to create a thermal spray of relatively dry particles in an intense vapor jet which issues from the capillary nozzle. The vaporization of the solution creates particles of solution which preferentially contain the molecules of interest to be analyzed. These particles are expelled at velocities up to and including supersonic velocity by the expanding vaporized solvent present in the capillary tube.